Ventricular size determination and management of ventriculomegaly and hydrocephalus in patients with diffuse intrinsic pontine glioma: an institutional experience

2021 ◽  
pp. 1-7
Author(s):  
Adriana Fonseca ◽  
Palma Solano ◽  
Vijay Ramaswamy ◽  
Uri Tabori ◽  
Annie Huang ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Univariate Analysis ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Survival Advantage ◽  
Ventricular Size ◽  
Pontine Glioma ◽  
Asymptomatic Patients ◽  
Institutional Experience ◽  
Csf Diversion ◽  
The Impact

OBJECTIVE There is no consensus on the optimal clinical management of ventriculomegaly and hydrocephalus in patients with diffuse intrinsic pontine glioma (DIPG). To date, the impact on survival in patients with ventriculomegaly and CSF diversion for hydrocephalus in this population remains to be elucidated. Herein, the authors describe their institutional experience. METHODS Patients diagnosed with DIPG and treated with up-front radiation therapy (RT) at The Hospital for Sick Children between 2000 and 2019 were identified. Images at diagnosis and progression were used to determine the frontal/occipital horn ratio (FOR) as a method to measure ventricular size. Patients with ventriculomegaly (FOR ≥ 0.36) were stratified according to the presence of symptoms and categorized as follows: 1) asymptomatic ventriculomegaly and 2) symptomatic hydrocephalus. For patients with ventriculomegaly who did not require CSF diversion, post-RT imaging was also evaluated to assess changes in the FOR after RT. Proportional hazards analyses were used to identify clinical and treatment factors correlated with survival. The Kaplan-Meier method was used to perform survival estimates, and the log-rank method was used to identify survival differences between groups. RESULTS Eighty-two patients met the inclusion criteria. At diagnosis, 28% (n = 23) of patients presented with ventriculomegaly, including 8 patients who had symptomatic hydrocephalus and underwent CSF diversion. A ventriculoperitoneal shunt was placed in the majority of patients (6/8). Fifteen asymptomatic patients were managed without CSF diversion. Six patients had resolution of ventriculomegaly after RT. Of 66 patients with imaging at the time of progression, 36 (55%) had ventriculomegaly, and 9 of them required CSF diversion. The presence of ventriculomegaly at diagnosis did not correlate with survival on univariate analysis. However, patients with symptomatic hydrocephalus at the time of progression who underwent CSF diversion had a survival advantage (p = 0.0340) when compared to patients with ventriculomegaly managed with conservative approaches. CONCLUSIONS Although ventriculomegaly can be present in up to 55% of patients with DIPG, the majority of patients present with asymptomatic ventriculomegaly and do not require surgical interventions. In some cases ventriculomegaly improved after medical management with steroids and RT. CSF diversion for hydrocephalus at the time of diagnosis does not impact survival. In contrast, our results suggest a survival advantage in patients who undergo CSF diversion for hydrocephalus at the time of progression, albeit that advantage is likely to be confounded by biological and individual patient factors. Further research in this area is needed to understand the best timing and type of interventions in this population.

scholarly journals DIPG-20. DETERMINATION AND MANAGEMENT OF HYDROCEPHALUS IN PATIENTS WITH DIPG, AN INSTITUTIONAL EXPERIENCE

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii291-iii291
Author(s):  
Adriana Fonseca ◽  
Palma Solano-Paez ◽  
Michal Zapotocky ◽  
Ute Bartels ◽  
Eric Bouffet
Keyword(s):  
Disease Progression ◽  
Univariate Analysis ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Proportional Hazard ◽  
Impact On Survival ◽  
Institutional Experience ◽  
Csf Diversion ◽  
Sick Children ◽  
The Impact

Abstract BACKGROUND The is no consensus in best practices for the management of hydrocephalus in patients with Diffuse Intrinsic Pontine Glioma (DIPG). To date, the impact on survival of hydrocephalus and Cerebro-Spinal Fluid (CSF) diversion in this population remains to be elucidated. Herein, we describe our institutional experience. METHODS Patients with a clinical and radiological diagnosis of DIPG were identified at the Hospital for Sick Children between 2000–2019. Images at diagnosis and at disease progression were assessed for hydrocephalus using the frontal-occipital ratio (FOR) method. Proportional hazard analyses were used to identify factors correlated with survival. RESULTS Eighty-nine consecutive patients diagnosed with DIPGs were treated at our institution. At diagnosis, 29% (n=26) of patients presented with hydrocephalus, seven patients underwent CSF diversion. Out of the remaining nineteen patients, n=6 had stable or improved hydrocephalus in follow-up scans, n=6 had persistent hydro and n=2 required CSF diversion at the time of disease progression. Seven did not undergo a follow-up scan. Out of sixty-five patients with imaging at the time of progression, fifty-five percent of patients (n=36) presented with hydrocephalus and ten of them required CSF diversion. On univariate analysis, the presence of hydrocephalus or CSF diversion at diagnosis and/or did not correlate with a survival advantage. CONCLUSIONS CSF diversion for the management of hydrocephalus in patients with DIPG does not impact survival and in some cases resolves spontaneously after the initiation of radiotherapy and steroids. This observation needs to be validated in a prospective cohort.

scholarly journals DIPG-25. KETOGENIC DIET IN DIFFUSE INTRINSIC PONTINE GLIOMA IN CHILDREN: A RETROSPECTIVE STUDY INVESTIGATING THE FEASIBILITY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii291-iii292
Author(s):  
Alexandre Perez ◽  
Janak Nathan ◽  
Moatasem El-Ayadi ◽  
Christian Korff ◽  
Marc Ansari ◽  
...  
Keyword(s):  
Ketogenic Diet ◽  
Controlled Trial ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Inclusion Criteria ◽  
Pontine Glioma ◽  
Randomized Controlled ◽  
Small Patient Population ◽  
Small Patient ◽  
The Impact ◽  
Aggressive Clinical Behavior

Abstract PURPOSE Diffuse Intrinsic Pontine Glioma (DIPG) is one of the most devastating diseases amongst children with cancer, thus novel strategies are urgently needed. We aimed to retrospectively evaluate the feasibility of the carbohydrate restricted ketogenic diet (KD) in DIPG patients. METHODS Searches of MEDLINE and Embase identified four publications meeting the inclusion criteria (diagnosis of DIPG and exposition to a KD ≥ 3 months). One additional case was identified by contact with experts. The minimal feasibility criteria were defined as the ability to use the KD for ≥ 3 months. Individual patient data were extracted from the publications or obtained from investigators. RESULTS Five patients (males, n=3; median age 4.4 years; range, 2.5–17 years) met the inclusion criteria (one patient – identified and not included - was on KD < 3 months due to disease progression). Further feasibility analyses showed a duration of the KD of ≥ 3 months and less than 7 months (n=2), > 7 months and less than 1 year (n= 2), and two years (n=1), respectively. CONCLUSION These results – based on a small patient population – suggest that the KD appears to be a feasible treatment option for children with DIPG. The potential duration of the KD is limited by the aggressive clinical behavior of DIPG. The safety analysis is currently being retrospectively assessed. These data should encourage further studies on a larger scale; ideally assessing the impact of the KD in DIPG patients in a randomized controlled trial.

scholarly journals Disparity in outcomes of melanoma adjuvant immunotherapy by demographic profile

2020 ◽  
Vol 7 (2) ◽  
pp. MMT43
Author(s):  
Alexandra Ikeguchi ◽  
Michael Machiorlatti ◽  
Sara K Vesely
Keyword(s):  
Survival Benefit ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Demographic Factors ◽  
Cox Proportional Hazards ◽  
Adjuvant Immunotherapy ◽  
Node Positive ◽  
Melanoma Patients ◽  
The Impact

Background: Randomized comparisons have demonstrated survival benefit of adjuvant immunotherapy in node-positive melanoma patients but have limited power to determine if this benefit persists across various demographic factors. Materials & methods: We assessed the impact of demographic factors on the survival benefit of adjuvant immunotherapy in a database of 38,189 node-positive melanoma patients using the Kaplan–Meier method and Cox proportional hazards models. Results: All assessed demographic factors other than race significantly impacted survival of node-positive melanoma patients in univariate analysis. In multivariable analysis, only the age group interacted with immunotherapy. Conclusion: Analysis of this large database of unselected node-positive melanoma patients demonstrated a positive survival benefit of immunotherapy across all demographic factors assessed and the impact was greater for patients 65 years of age and older.

Optimal timing of radical cystectomy after neoadjuvant chemotherapy in muscle invasive bladder cancer (MIBC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 509-509
Author(s):  
Saurabh Parasramka ◽  
Janeesh Sekkath Veedu ◽  
Quan Chen ◽  
Bin Huang ◽  
Peng Wang ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Survival Benefit ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Optimal Timing ◽  
Current Standard ◽  
Time Period ◽  
The Impact

509 Background: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with bilateral pelvic lymph node dissection is the current standard of care for MIBC. Pathologic downstaging with NAC is an important surrogate endpoint and associated with overall survival benefit. There have been questions about the impact of delay in definitive surgery because of NAC. The optimal timing of surgery from the start of NAC is uncertain. We studied this question using National Cancer Database (2004-2015). Methods: We identified patients with MIBC (cT2-T4aN0M0 & cT1-T4aN1M0) who received NAC within 6 months of diagnosis and underwent surgery between 10 weeks and 9 months of the start day of NAC. We excluded patients who died within 30 days of surgery. Time period was stratified into three cohorts; 11-16, 17-24, and ≥25 weeks from the start day of NAC. Descriptive analysis, Kaplan-Meier plots, Log-Rank tests for univariate and proportional hazards models for multivariate survival analyses were performed. Results: 3709 patients were identified; 75% were males, 77% cases were cT2 and 73% had charlson-deyo score (CS) of '0'. Median time for surgery 10 weeks after start of NAC was 118 days. Forty-two (42%) had surgery in 11-16, 47% in 17-24 and 9.9% in ≥25 weeks. Majority (60%) were treated at academic and 24% at comprehensive community. Only 29% achieved complete pathological complete response rate (Tis or T0). On univariate analysis receiving NAC within 3 months of diagnosis was significantly associated with survival benefit (p < 0.001). Cox-regression results showed that patients who underwent surgery in 11-16 and 17-24 week time period had significantly better survival than > 25 week group with HR of 0.84 (0.71- 0.98) and 0.82 (0.70-0.97) respectively. In addition patients with CS of '0' had better survival with HR 0.78 (0.62-0.90) and > 75 years of age was associated with worse survival HR 1.73 (1.35-2.22). Conclusions: Our study indicates that appropriate patients with MIBC benefit from receiving surgery within 24 weeks of starting NAC. However, randomized prospective study is warranted to further explore the role of delay of surgery from NAC.

scholarly journals Histone tail analysis reveals H3K36me2 and H4K16ac as epigenetic signatures of diffuse intrinsic pontine glioma

2020 ◽  
Author(s):  
Shejuan An ◽  
Jeannie Camarillo ◽  
Tina Huang ◽  
Daphne Li ◽  
Juliette Morris ◽  
...  
Keyword(s):  
Cell Lines ◽  
Radiation Treatment ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Response To Treatment ◽  
Wild Type ◽  
Post Translational Modification ◽  
Pontine Glioma ◽  
Epigenetic Signatures ◽  
The Impact

Abstract Background: Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brainstem tumor. Most DIPGs harbor a histone H3 mutation, which alters histone post-translational modification (PTM) states and transcription. Here, we employed quantitative proteomic analysis to elucidate the impact of the H3.3K27M mutation, as well as radiation and bromodomain inhibition (BRDi) with JQ1, on DIPG PTM profiles.Methods: We performed targeted mass spectrometry on H3.3K27M mutant and wild-type tissues (n=12) and cell lines (n=7).Results: We found 29.2% and 26.4% of total H3.3K27 peptides were H3.3K27M in mutant DIPG tumor cell lines and tissue specimens, respectively. Significant differences in modification states were observed in H3.3K27M specimens, including at H3K27, H3K36, and H4K16. In addition, H3.3K27me1 and H4K16ac were the most significantly distinct modifications in H3.3K27M mutant tumors, relative to wild-type. Further, H3.3K36me2 was the most abundant co-occurring modification on the H3.3K27M mutant peptide in DIPG tissue, while H4K16ac was the most acetylated residue. Radiation treatment caused changes in PTM abundance in vitro, including increased H3K9me3. JQ1 treatment resulted in increased mono- and di-methylation of H3.1K27, H3.3K27, H3.3K36 and H4K20 in vitro. Conclusion: Taken together, our findings provide insight into the effects of the H3K27M mutation on histone modification states and response to treatment, and suggest that H3K36me2 and H4K16ac may represent unique tumor epigenetic signatures for targeted DIPG therapy.

scholarly journals Histone tail analysis reveals H3K36me2 and H4K16ac as epigenetic signatures of diffuse intrinsic pontine glioma

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Shejuan An ◽  
Jeannie M. Camarillo ◽  
Tina Yi-Ting Huang ◽  
Daphne Li ◽  
Juliette A. Morris ◽  
...  
Keyword(s):  
Cell Lines ◽  
Radiation Treatment ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Response To Treatment ◽  
Wild Type ◽  
Post Translational Modification ◽  
Pontine Glioma ◽  
Epigenetic Signatures ◽  
The Impact

Abstract Background Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brainstem tumor. Most DIPGs harbor a histone H3 mutation, which alters histone post-translational modification (PTM) states and transcription. Here, we employed quantitative proteomic analysis to elucidate the impact of the H3.3K27M mutation, as well as radiation and bromodomain inhibition (BRDi) with JQ1, on DIPG PTM profiles. Methods We performed targeted mass spectrometry on H3.3K27M mutant and wild-type tissues (n = 12) and cell lines (n = 7). Results We found 29.2 and 26.4% of total H3.3K27 peptides were H3.3K27M in mutant DIPG tumor cell lines and tissue specimens, respectively. Significant differences in modification states were observed in H3.3K27M specimens, including at H3K27, H3K36, and H4K16. In addition, H3.3K27me1 and H4K16ac were the most significantly distinct modifications in H3.3K27M mutant tumors, relative to wild-type. Further, H3.3K36me2 was the most abundant co-occurring modification on the H3.3K27M mutant peptide in DIPG tissue, while H4K16ac was the most acetylated residue. Radiation treatment caused changes in PTM abundance in vitro, including increased H3K9me3. JQ1 treatment resulted in increased mono- and di-methylation of H3.1K27, H3.3K27, H3.3K36 and H4K20 in vitro. Conclusion Taken together, our findings provide insight into the effects of the H3K27M mutation on histone modification states and response to treatment, and suggest that H3K36me2 and H4K16ac may represent unique tumor epigenetic signatures for targeted DIPG therapy.

Analysis of factors influencing outcome in patients with in transit malignant melanoma (MM) undergoing isolated limb perfusion (ILP) using standardized operative parameters with melphalan and biological agents

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8006-8006
Author(s):  
P. A. Soriano ◽  
S. K. Libutti ◽  
J. F. Pingpank ◽  
T. Beresenev ◽  
S. M. Steinberg ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Cox Model ◽  
Univariate Analysis ◽  
Female Gender ◽  
Tumor Stage ◽  
Cox Proportional Hazards ◽  
Stage Iiia ◽  
In Transit ◽  
The Impact

8006 Background: In transit disease afflicts about 10% of MM patients and no single systemic or regional treatment has been widely accepted as most effective or appropriate. Previously, the impact of ILP on the natural history of MM patients has been difficult to gauge. We report long-term outcomes in MM patients undergoing hyperthermic ILP in an era of increasingly accurate staging, uniform operative and treatment conditions, and regular follow-up. Methods: Between 5/1992 to 2/2005, 90 patients (median age: 57 y [range: 24–84]; F: 49, M: 41) with Stage IIIA or IIIAB MM underwent a 90 min hyperthermic (mean calf T: 39.3° C) ILP (melphalan: 10–13 mg/L limb volume, TNF: 3–6 mg [n=44], or IFN: 200 μg [n=38]) using uniform operative technique including intra-operative leak monitoring. There was 1 operative mortality (1/91, 1.1%). Patients were prospectively followed for response, in-field progression free (PFS), and overall survival (OS). Parameters associated with in-field PFS and OS were analyzed by the Kaplan-Meier method with log rank tests, as well as by Cox proportional hazards models. Results: There were 61 complete responses (68%) and 23 partial responses (26%). At a median follow-up of 47 months, median in-field PFS was 12.4 months, and median OS was 47.4 months; 5 and 10-year actuarial OS were 43 and 34%, respectively. Female gender and low tumor burden (< 20 tumors) were associated with prolonged in-field PFS (M:F hazard ratio (HR): 2.07, CI:1.27–3.38; 21+ vs. ≤20 tumors HR: 2.29, CI: 1.21- 4.34; p<0.011 for both) in a Cox model, whereas TNF, IFN, perfusion pressure, and tumor stage were not. Female gender was associated with improved OS (p=0.027, M:F HR=1.82, 95% CI 1.07–3.09) and Stage IIIA marginally so, in univariate analysis, (p=0.065). Conclusions: ILP for MM patients is associated with noteworthy in-field PFS and prolonged OS. Neither use of TNF nor tumor stage were significantly associated with in-field PFS in Cox models, while female gender was associated with better outcomes. In appropriately selected patients using standardized technique, ILP has clinical benefit in this setting. No significant financial relationships to disclose.

Multicenter analysis of 81 solid organ transplant (SOT) recipients with posttransplantation lymphoproliferative disease (PTLD): Examination of survival and prognostic factors

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8510-8510
Author(s):  
A. M. Evens ◽  
K. A. David ◽  
I. Helenowski ◽  
S. M. Kircher ◽  
L. Mauro ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Proportional Hazards ◽  
Large Population ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Organ Transplant ◽  
Lymphoproliferative Disease ◽  
Cox Proportional Hazards ◽  
Solid Organ ◽  
The Impact

8510 Background: PTLD has a reported 3-year (yr) overall survival (OS) of 35–40% (Leblond, JCO 2001). The impact of rituximab (RTX) on the prognosis or outcome of PTLD is not known. Methods: We examined the clinical features, treatment, and outcomes among a large population-based cohort of SOT-related PTLD patients (pts) at 4 Chicago institutions (1/98–2/08). Prognostic factors were evaluated in univariate and Cox proportional hazards regression for survival. Results: 81 PTLD pts were identified (SOT: 47 kidney ± pancreas, 4 pancreas, 17 liver, 8 heart, 5 lung) with median age at diagnosis (dx) of 48 yrs (range 20–72). Median time from SOT to PTLD was 42 months (mo) (range 1–216 mo). PTLD dx (per WHO) were 55 monomorphic, 22 polymorphic and 4 plasmacytic, while 42 were EBV+ and 30 EBV-negative (9 unknown). 74% of pts (60/81) were treated with rituximab ± chemotherapy (and reduction of immune suppression). With 38-mo median followup for all pts, 3-yr progression-free (PFS) was 58% and 3-yr OS 62%, despite 16% of pts dying ≤ 6 weeks from dx. Most relapses (30/32) occurred ≤ 12 months from dx. Pts receiving RTX as part of therapy had 3-yr PFS of 69% and OS 71% (vs 21% (p=0.0002) and 33% (p=0.001), respectively, without RTX). Univariate analysis identified prognostic factors for PFS/OS (all <0.01): 1) PS, 2) serum albumin, 3) >1 EN site, 4) marrow involvement, 5) CNS disease and 6) RTX as part of initial therapy. Neither histology nor EBV status predicted outcome. On multivariate analysis, 4 factors remained significant ( Table 1a ). Further, a survival model based on 3 factors was constructed ( Table 1b ). Conclusions: This study represents the largest PTLD report in RTX-treated pts. We are the first to identify the prognostic significance of low albumin and a low PTLD relapse rate beyond 1 yr (6.3%). Further, it appears that the introduction of RTX has improved the survival of PTLD. In addition, clinical factors at dx identified pts with markedly divergent outcomes. [Table: see text] [Table: see text] No significant financial relationships to disclose.

Association of multidimensional comorbidities with survival in elderly patients with metastatic colorectal cancer treated with chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21530-e21530
Author(s):  
Ki Hyang Kim ◽  
Jae Jin Lee ◽  
Jongphil Kim ◽  
Fabio Renato Morgado Gomes ◽  
Marina Sehovic ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Proportional Hazards ◽  
Rating Scale ◽  
Univariate Analysis ◽  
Cox Proportional Hazards ◽  
Age At Diagnosis ◽  
Cancer Center ◽  
Ecog Ps ◽  
The Impact

e21530 Background: In geriatric assessments, comorbidity is often assessed with tools such as the Charlson comorbidity index (CCI) and the Cumulative Illness Rating Scale-Geriatrics (CIRS-G). In studies of older patients with colorectal cancer (CRC), comorbidity was mainly measured using the CCI, and inconsistent results about the correlation comorbidity with overall survival (OS) were found. In order to refine our understanding of the impact of comorbidity, we evaluated its correlation with OS using the CIRS-G and heat maps to elicit the subgroups with the highest impact. Methods: We retrospectively reviewed 153 consecutive patients from the Total Cancer Care database, aged ≥65 with stage 4 CRC, who underwent chemotherapy at Moffitt Cancer Center from 2000 to 2015. The association between CIRS-G scores and OS was examined by the Cox proportional hazards regression model. Results: Median age at diagnosis was 71 years. Forty-eight % of patients had an ECOG PS of 0. Median MAX2 score of chemotherapies was 0.119. Median total score of CIRS-G was 8 (1-20) and median severity index was 0.57 (0.07-1.43). The most common comorbidities were vascular, EENT and larynx, and respiratory diseases. Eleven patients had 1 comorbidity and 1 patient had 2 comorbidities at level 4 severity. Median OS of all patients was 25.1 months (95% CI 21.2-27.6). In univariate analysis, the number of CIRS-G level 4 comorbidities was a significant worse prognostic factor for OS (0 vs 1 or 2, HR 2.16, p = 0.017). In multivariate analysis, ECOG PS ≥2, poorly differentiated histology, age at diagnosis and numbers of CIRS-G level 4 comorbidities were significant worse prognostic factors for OS. ECOG PS ≥2 and age at diagnosis were significant worse prognostic factors for unplanned hospitalization. Conclusions: The OS in the elderly metastatic CRC patients was good and similar to the general population with this disease. The number of CIRS-G level 4 comorbidities was associated with worse OS but no specific CIRS-G category was individually associated with OS.

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